rs1053639

Positions:

• chr10-72275283-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019058.4(DDIT4):​c.*95T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,395,196 control chromosomes in the GnomAD database, including 106,227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11752 hom., cov: 32)
  • Exomes 𝑓: 0.38 (94475 hom.)
• Consequence: DDIT4 NM_019058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

Genes affected

DDIT4 (HGNC:24944): (DNA damage inducible transcript 4) Predicted to enable 14-3-3 protein binding activity. Involved in defense response to virus; negative regulation of TOR signaling; and response to hypoxia. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDIT4	NM_019058.4	c.*95T>A		3_prime_UTR_variant	3/3	ENST00000307365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDIT4	ENST00000307365.4	c.*95T>A		3_prime_UTR_variant	3/3	1	NM_019058.4	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56809 AN: 151936 Hom.: 11730 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.379 AC: 471182 AN: 1243142 Hom.: 94475 Cov.: 18 AF XY: 0.379 AC XY: 232069 AN XY: 612138

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.772

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.518

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.374 AC: 56863 AN: 152054 Hom.: 11752 Cov.: 32 AF XY: 0.388 AC XY: 28840 AN XY: 74322

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.358

Alfa AF: 0.371 Hom.: 1460

Bravo AF: 0.362

Asia WGS AF: 0.611 AC: 2128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	17
DANN	Benign	0.59
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1053639; hg19: chr10-74035041;